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Tuberculosis (Edinb). 2011 Jan;91(1):36-46. doi: 10.1016/j.tube.2010.11.008. Epub 2010 Dec 13.

PD-L2 induction on dendritic cells exposed to Mycobacterium avium downregulates BCG-specific T cell response.

Author information

1
Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Edificio de Investigación 4 piso, Facultad de Medicina- Universidad Nacional Autonoma de México, Av. Universidad #3000, Coyoacán, 04630 México, DF Mexico.

Abstract

The exposure to certain species of Nontuberculous Mycobacteria (NTM) can modulate the immune response induced by Mycobacterium bovis BCG. Mycobacterium avium has been postulated as a weak inducer of dendritic cell (DC) maturation. However, how the DC exposure to M. avium could contribute to the modulation of a BCG-specific CD4+ T cell response and the molecules involved remain unknown. Here, we exposed bone marrow-derived DCs (BMDCs) to M. avium either prior to exposure to BCG or as a unique stimulus. We found that M. avium induces high expression of PD-L2 (B7-DC) in BMDCs. This was dependent on IL-10 production through the TLR2-p38 MAPK signaling pathway. Exposure to M. avium prior to BCG results in BMDCs that do not express co-stimulatory molecules and pro-inflammatory cytokines, while the expression of PD-L2 and IL-10 was maintained. BMDCs exposed to M. avium impaired the activation of BCG-specific T cells through the PD-1: PD-L interaction. This suggests that a M. avium-induced phenotype in DCs might be implicated in the induction of mechanisms of tolerance that could impact the T cell response induced by BCG vaccination.

PMID:
21147037
DOI:
10.1016/j.tube.2010.11.008
[Indexed for MEDLINE]

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